Cancer of the large bowel is second only to lung cancer as the major malignant disease in the U.S.A. Our research program is designed to carry out studies on the etiology of large bowel cancer. This will be done by delineating the relationship between intestinal bacteria, nitrosamines and nitrosamides, and large bowel cancer as follows: a) germ-free and conventional rats will be used to develop a useful model system for studying colon carcinogenesis by assessing and comparing the capacity of selected nitrosamines and nitrosamides to produce colonic tumors; b) both conventional and gnotobiotic BD or Buffalo rats, which are known to develop cancers of the large bowel in response to treatment with various carcinogens, will be compared to Sprague-Dawley rats treated in the same way; c) studies will be carried out to determine if nitrates and/or nitrites are in the large bowel and d) we will study the capacity of carcinogens to alkylate macromolecules in the large bowel of Sprague-Dawley, BD, and Buffalo rats. These studies will result in an animal model, precursor compounds, and a carcinogen that will be related to large bowel cancer in man.